1. Field of the Invention
The invention relates to a small peptide and specifically to imaging and treatment of a non-small cell lung cancer.
2. Description of the Related Art
Lung cancer is one of the most common cancers and is the leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. There are three types of cancer that are considered NSCLC including adenocarcinoma, squamous cell carcinoma (SCC), and large cell undifferentiated carcinoma. Approximately three quarters of patients with lung cancer have an advanced stage of tumor at the time of diagnosis. The most recent statistics show the overall five-year survival of lung cancer is about 10% to 16% in the United States, Europe and China after diagnosis. The survival of lung cancer is heavily dependent on early diagnosis. For example, 5-year survival of Stage IA/B lung cancer is approximately 70% and for Stage IIA/B disease is in the range of 50% when patients are eligible to receive surgery. Therefore, early detection improves apparent survival of lung cancer patients, even if mortality remains unchanged.
Globally, imaging such as PET/CT or single-photon emission computed tomography (SPECT) remains the most effective methods for lung cancer detection. Unfortunately, these current scanning modalities are not sufficiently sensitive or specific to clearly determinate between benign and malignant solitary pulmonary nodules. The false-positive imaging may happen in inflammation (e.g., pneumonia and active tuberculosis) and granulomatous disease (e.g., sarcoidosis and Wegener's granulomatosis) because these pulmonary nodules have the same high uptake of FDG as malignancy. Meanwhile, limitations of PET/CT for evaluating lung nodules are a reduction in specificity and increased false negatives in very small tumors or those with low FDG uptake (e.g., bronchoalveolar carcinomas) (Maffione A M, et al. J Nucl Med. 2014; 55: 983-988). SPECT is widely available, has lower costs than PET/CT, and does not require the presence of a cyclotron adjacent to the hospital. Encouraging results have been obtained with SPECT scanning using sestamibi to detect primary lung malignancies and to perform mediastinal staging with a higher diagnostic accuracy higher than chest CTs. However, the main difficulty is related to the limited spatial resolution of SPECT. To overcome the limited resolution of SPECT, many investigators are working on developing novel sensitive and specific radiotracers for SPECT.
Application for molecularly targeted agents in a non-small cell lung cancer (NSCLC) has witnessed swift evolution in the last decade. These targeted anticancer agents promise more efficient and less toxic side effects for patients as compared with common chemotherapeutic agents. The EGF receptor (EGFR) is therapeutically targeted by antibodies (Cetuximab) and small molecules (Iressa, erlotinib) in solid tumors including lung, colorectal, and breast cancer. However, a small percentage of patients (21%) with an EGFR mutation have higher response rates and all patients eventually develop resistance. Another promising approach has been obtained in radioimmunotherapy (RIT) for the treatment of B-cell non-Hodgkin's lymphoma with yttrium-90 (90Y)-ibritumomabtiuxetan (Zevalin) and iodine-131 (131I)-tositumomab (Bexxar). 131I-chTNT is the first approved clinical trial radiolabeled antibody for the treatment of solid tumors including lung cancer, glioblastoma, head and neck cancer, colorectal carcinoma, hepatocellular carcinoma, etc. However, the response rate (ORR) was only 33% in non-small-cell lung cancer patients (Chen S, et al. J Clin Oncol. 2005; 23: 1538-47). 131I-chTNT was iodine-131-labeled recombinant human and mouse chimeric TNT antibody and has potential allergen. It is, therefore, essential to seek more effective and less toxic modes of therapy for advanced lung cancer.